Data communication and control for medical imaging systems

ABSTRACT

A system for producing a contrast-enhanced medical image of a patient includes a source of a contrast or enhancement medium, a pressurizing unit in fluid connection with the source of contrast or enhancement medium, an energy source operable to apply energy to a region of the patient, an imaging unit providing a visual display of an internal view of the patient based upon a signal resulting from the energy applied to the region of the patient, and a control unit. In an embodiment, the signal is affected by a condition of the contrast or enhancement medium in the patient. To control the procedures, the control unit adjusts the condition of the contrast or enhancement medium in the patient based upon the signal. A communication interface preferably enables information between an injector subsystem and an imaging subsystem.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 09/300,326, filed on Apr. 27, 1999, now U.S. Pat. No. 6,397,098which is a continuation-in-part of U.S. patent application Ser. No.09/197,773, filed on Nov. 23, 1998, now U.S. Pat. No. 6,385,483 which isa divisional of U.S. patent application Ser. No. 08/309,820, filed onSep. 21, 1994, now U.S. Pat. No. 5,840,026, the disclosures of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION

The present invention relates generally to data communication andcontrol, and, more particularly, to devices, systems and methods forcommunication of data and control based thereon in contrast-enhancedmedical imaging systems.

It is well recognized that the appropriate dose for many medications isrelated to a number of variables, including, for example, the size,weight, or physiologic state of the patient being treated. Thisvariation is readily apparent from the different recommended doses manymedications have for adults and children. The appropriate dose ofcontrast media for a given medical imaging procedure is equallydependent upon the size and weight of the patient being examined as wellas additional factors.

Although differences in dosing requirements for medical imagingprocedures have been recognized, many conventional medical imagingprocedures, including angiographic, computed tomography, magneticresonance and ultrasound imaging, continue to use pre-set doses orstandard delivery protocols for injecting contrast media during medicalimaging procedures. Although using fixed protocols for deliverysimplifies the procedure, providing the same amount of contrast media topatients of widely varying size and weight can produce very differentresults in image contrast and quality.

Some of the shortcomings of existing procedures have been addressed andresolved as described in U.S. Pat. No. 5,806,519, issued Sep. 15, 1998,the disclosure of which is incorporated herein by reference. U.S. Pat.No. 5,806,519 discloses a contrast media delivery system that provides asource of contrast media sufficiently isolated from a patient undergoingan imaging procedure that the source of contrast media may be used onadditional patients without concern for contamination. Additionally, thesystem is capable of adjusting contrast media concentration and otherinjection parameters during an injection procedure. The term“concentration” refers generally to the concentration of the imageenhancing agents, particles or chemicals, in the contrast media.

The system of U.S. Pat. No. 5,806,519 incorporates a source of contrastmedia and, if desired, an admixture to dilute the media. If there is anadmixture, then the contrast media preferably has a concentration whichis the highest that would be used in an injection procedure so that theoperator may combine the contrast media with the admixture and selectvirtually any concentration of contrast media desired for any givenprocedure. The concentration of the contrast media injected into apatient may be varied during the injection procedure by varying theratio of admixture to contrast media. Each patient thus receives onlythe amount of contrast media necessary to provide a proper diagnosticimage.

It has been recognized that the system of U.S. Pat. No. 5,806,519 ismuch more versatile and useful if the operator is able to select andadjust contrast media concentration and other injection parameters basedon patient information and/or feedback received during the injectionimaging procedures. U.S. patent application Ser. No. 09/197,773 and U.S.Pat. No. 5,840,026 disclose such systems. Those systems are capable ofautomatically choosing the appropriate concentration and injection ratefor a given patient and are capable of automatically adjustingconcentration and other injection parameters during an injectionprocedure based on feedback related to the resultant image quality.

Although significant strides have thus been achieved in the control ofcontrast-enhanced, medical imaging procedures, it remains desirable todevelop improved devices, systems and methods for communication of databetween devices and control based thereon in contrast-enhanced medicalimaging systems.

SUMMARY OF THE INVENTION

The present invention provides several systems, devices and methods forproducing a contrast-enhanced medical image of a patient. According toone embodiment, such a system includes generally a source of a contrastor enhancement medium and a pressurizing unit in connection with thesource of contrast or enhancement medium to pressurize the contrast orenhancement medium for injection into the patient. The contrast mediumor enhancement medium is also called the fluid medium, being a liquid,gas, or solid suspended in a liquid or a gas. The system also includesan energy source adapted to apply energy to a region of the patient andan imaging unit providing (preferably in real-time) an indication (forexample, a visual or audible indication) of an internal state, conditionor view of the patient based upon a signal resulting from the energyapplied to the region of the patient. This signal is affected by acondition of the contrast or enhancement medium in the patient. Thesystem also includes a control unit adapted to adjust the condition ofthe contrast or enhancement medium in the patient based upon the signalresulting from the energy applied to the region of the patient. Thesystem may include general components or pieces of equipmentmanufactured by more than one company, for instance, an injector and animager.

The condition of the fluid medium flowing into the patient can, forexample, correspond to at least one parameter including, but not limitedto, contrast medium concentration, flow rate of the contrast medium,timing of an injection, sequencing of more than one injection (of thesame or different contrast media), injected volume of the contrastmedium, injection pressure of the contrast medium or temperature of thecontrast medium.

Although U.S. Pat. No. 5,840,026 describes generally the use of thepixel intensity of one or more portions or regions of the visual displayof an imaging unit to control one or more conditions of the fluid mediumwithin the patient, the present inventors have also discovered thatdirect use or modification of the raw signal used to produce the imagemay have certain significant advantages in controlling the imagingprocedure. For example, a portion of the information available from theraw signal may be lost or distorted in various compression algorithmsthat are used to address the limited dynamic range of the displays thatare available to show an image. The energy applied to the region of thepatient may, for example, be sonic energy, in which case the raw signalis an acoustic intensity signal. This particular method is sometimescalled acoustic intensitometry or acoustic densitometry. The energy may,for example, also be penetrating radiation such as X-rays, ornon-ionizing electromagnetic radiation such as light.

The present invention also provides another embodiment of a system forproducing a contrast-enhanced medical image of a patient including asource of a fluid medium and a pressurizing unit as described above. Asused herein, the terms “image” or “view” refer generally to anindication of an internal condition or state of a patient and are notlimited to a visual display. The system also includes an energy sourceand an imaging unit to provide (preferably in real-time) an indication(for example, a visual display) of an internal view of the patient basedupon a signal resulting from the energy applied to the region of thepatient. In this embodiment, the system further includes a control unitadapted to adjust the condition (as described above) of the fluid mediumin the patient to maintain at least one portion of the indication (forexample, a portion of a visual display) at a desired level of intensityor enhancement. For example, the control unit can adjust the conditionof the fluid medium flowing into the patient based upon the signalresulting from the imaging energy applied to the region of the patient.The system can also adjust the condition of the fluid medium flowinginto the patient based upon measured intensity or density of the portionof a visual display. Such control of the imaging procedure assists inthe study of, for example, lesions in the region of interest.

In another embodiment, the control unit adjusts parameters of theimaging unit to obtain an optimum or sufficient image based upon theconcentration of the contrast-enhancing agent flowing into the patient.Possible adjusted parameters include but are not limited to: the powerin the signal sent into the patient, the time during which the energy isapplied to the patient, the gain of the amplifier which receives thesignal from the patient, or the speed at which the energy is scannedacross the patient.

The present invention also provides a system for delivering an activesubstance (for example, a biologically active therapeutic substance or adiagnostic substance) to a patient including a source of a fluid mediumthat incorporates the active substance and a contrast agent. Apressurizing unit is in fluid connection with the source of fluid mediumto pressurize the fluid medium for injection into the patient. Thesystem also includes an imaging energy source adapted to apply imagingenergy to a region of the patient and an imaging unit providing a visualdisplay (preferably in real-time) of an internal view of the patientbased upon a signal resulting from the imaging energy applied to theregion of the patient. The system further includes a control unitadapted to control delivery of the active substance by adjusting thecondition of the contrast agent in the patient.

In this embodiment, the active substance is preferably activated byactivation energy from a source of activation energy. The activationenergy and the imaging energy can be the same or different types ofenergy. In general, the concentration of the active substance in aregion of interest will be directly proportional to the concentration oramount of contrast agent in the region of interest. The strength andduration of the applied activation energy can, for example, be adjustedbased upon the signal resulting from the imaging energy or upon theresulting visual or other (for instance sound pitch, sound volume,numeric readout, or meter readout) indication provided to the user(preferably in real-time). The contrast medium and the active substancemay be combined. For example, a therapeutic drug or a gene therapy maybe contained in partially gas filled microspheres that are ruptured byultrasound energy beamed into a specific part of the body to activatethe therapeutic drug or gene therapy.

The present invention further provides another system for producing acontrast-enhanced medical image of a patient similar to the systemsdescribed above. In this embodiment, however, the control unit isadapted to time injection of at least one discrete flow interval offluid medium based, for example, upon at least one of a visual displayor a signal resulting from application of the imaging energy to a regionof the patient (both may be used simultaneously). In one embodiment, thediscrete flow interval may be a bolus of fluid medium.

Preferably, unidirectional or bi-directional communication andoptionally control between devices of the present invention is enabledthrough use of a control/communication interface to which each of thedevices of the imaging/injection system can be connected. This interfacemating point can be located on a separate device or can be incorporatedinto one of the other devices (for example, into a controller for thepressurizing unit or injector). Suitable communication methods includedata transmission, preferably digital, over wires, fiber optics, or viaconducted or broadcast electromagnetic radiation (for example, light andRF) or ultrasonic radiation.

The communication interface of the present invention is a substantialimprovement over previous systems that merely communicated timinginformation via relay closures. In the present invention, datatransmission includes information sent between devices regardingoperating parameters, operator input, device status information, and/orcontrol sequencing. In addition, data transferred from one device toanother device in the present invention can be used to enable activecontrol of the receiving device from that data. For example, during theinjecting state, data transmission from an ultrasound imager can be sentto an injector to enable active control of the injection flow rate basedon the data received. Currently available systems merely relay analogclosures between an injector and an imager to communicate the timing ofcertain states and are not used for data transmission or communication.In such systems, the relay closure causes the injector or imagersubsystem to begin executing a preset program. In the present inventionon the other hand, data on the status of one subsystem is communicatedto the other subsystem for use by that subsystem. The receivingsubsystem may alter its operation based upon this information, even tothe extent of being programmed by the transmitting subsystem. Moreover,digital communication enabled by the present invention allows much moreinformation to be conveyed than a simple relay closure.

Preferably the communicating devices use the same protocol so that theinformation being communicated does not need to be converted. Note thatit is also possible for the devices to support multiple communicationprotocols, which may be selected by the user or selected by automaticnegotiation between the communicating devices.

In addition, the present invention provides methods for adjusting thecondition of a fluid medium (as described above) during an imagingprocedure. In one embodiment, the method includes pressurizing the fluidmedium for injection into the patient. Further, the method includessupplying energy to a region of the patient and indicating (preferablyin real-time) an internal view (that is, a condition or state) of thepatient based upon a signal resulting from the energy applied to theregion of the patient. This signal is affected by a condition of thefluid medium in the patient as described above. The method furthercomprises the step of adjusting the condition of the fluid medium in thepatient based upon the signal resulting from the energy applied to theregion of the patient.

In another method, the condition of the fluid in the patient is adjustedto maintain at least one portion of the indication (for example, aportion of a visual display) at a desired level of intensity/density orintensity/density profile over time. For example, the control unit canadjust the condition of the fluid medium in the patient based upon thesignal resulting from the energy applied to the region of the patient toprovide enhancement in the region of interest that is constant or varieswithin some acceptable range. The system can also adjust the conditionof the fluid in the patient based upon measured intensity of the portionof a visual display or measured intensity of an acoustic indicator. Asdiscussed above, such control of the imaging procedure can assist, forexample, in the study of lesions in the region of interest.

The present invention also provides a method for delivering an activesubstance to a patient, comprising the step of controlling delivery oradministration of the active substance by adjusting the condition of thecontrast agent in the patient. As described above, the active substanceis preferably activated by activation energy from a source of activationenergy. The activation energy and the imaging energy can be the same ordifferent types of energy.

The present invention also provides for structured communications in thesituation where the control unit functions are shared between two ormore pieces of equipment.

For example, the present invention provides a system for control of animaging procedure comprising: a source of a contrast or enhancementmedium; a pressurizing unit in fluid connection with the source ofcontrast or enhancement medium to pressurize the contrast or enhancementmedium for injection of the contrast or enhancement medium into thepatient; an imaging energy source adapted to apply imaging energy to aregion of the patient; an imaging unit providing an indication (forexample, a visual display) of an internal view of the patient based upona signal resulting from the imaging energy applied to the region of thepatient, the signal being affected by a condition of the contrast orenhancement medium in the patient; and a data communication interfacebetween at least the pressurizing unit and the imaging unit to enableexchange of data between the pressurizing unit and the imaging unit.Preferably, the exchange of data is bi-directional. Moreover, the datais preferably in digital form.

The present invention also provides an injector system for producing acontrast-enhanced medical image of a patient in cooperation with animaging system. As described above, the imaging system applies energy toa patient and produces an image or a measurement of a region of interestin the patient from a signal resulting from the applied energy. Theinjector system preferably comprises: a source of a contrast orenhancement medium; a pressurizing subsystem in connection with thesource of contrast or enhancement medium to pressurize the contrast orenhancement medium for injection into the patient; an injector controlunit for controlling said pressurizing subsystem; and a communicationinterface to exchange data between the injector system and the imagingsystem.

The injector system may communicate information from the injector systemto the imaging system. Likewise, the imaging system may communicate dataor information from the imaging system to the injector system. Suchcommunication can be unidirectional or bi-directional. The injectorcontrol unit may modify one or more parameters of the injection basedupon the data or information from the imaging system. The imagingcontrol unit may also modify one or more parameters of the imager unitbased on the data or information sent from the injector. The injectorsystem may further contain an electrically and/or physically isolated(wireless) interface through which the communication interface exchangesdata or information with the imaging unit.

The present invention also provides an imaging unit for producing acontrast-enhanced medical image of a patient in cooperation with aninjector system. As described above, the injector system pressurizes acontrast or enhancement medium for injection into the patient. Theimaging unit preferably comprises: a source of energy to be applied to aregion of interest in the patient; a display to provide an image basedupon a signal resulting from the imaging energy applied to the region ofthe patient; an imaging control unit for controlling the imaging unit;and a communication interface to exchange data or information betweenthe injector system and the imaging unit.

Communication of data/control may be from the injector system to theimaging unit or visa versa and either uni- or bi-directional. Theimaging unit preferably further contains an electrically and/orphysically isolated interface through which the communication interfaceshares information with the injector system.

The interface is preferably in communicative connection with at leastthe pressurizing unit and the imaging unit to enable sharing andexchanging of data between the pressurizing unit and the imaging unit.

The above and other systems, devices and methods of the presentinvention, and their attendant advantages, will become even moreapparent to one skilled in the art upon consideration of the followingdetailed description in combination with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an embodiment of an injection and imaging system ofthe present invention using ultrasonic energy to display an image of aninternal region of the patient.

FIG. 2 illustrates an embodiment of a data communication unit of thepresent invention.

FIG. 3 illustrates another embodiment of an injection and imaging systemof the present invention.

FIG. 4 illustrates an example of internal transmit and receive sequencenumbering.

FIG. 5 illustrates an embodiment of a connection between an injectionsystem and external device, showing physical layer control signals.

FIG. 6 illustrates an embodiment of the communications protocol betweenan injector system and external device, showing message flow control.

FIG. 7 illustrates an example of a state transition diagram of thereceive processing to be performed by an external device communicatingwith an injector subsystem of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be discussed, in part, with reference to amodel injection and imaging system 10 illustrated in FIG. 1, in whichultrasonic energy is applied to a patient 20 to display an image of aninternal region of patient 20. However, it should be understood that thepresent invention is also applicable to other imaging modalities,including x-ray, computed tomography, magnetic resonance imaging,nuclear imaging, and other modalities in which energy is released withinor transmitted through a portion of the human body, animal, or otherobject to be indicated or imaged.

Ultrasound imaging creates images of the inside of the human body bybroadcasting ultrasonic energy into the body and analyzing the reflectedultrasound energy. Differences in reflected energy appear as differencesin gray scale or color on the output images. As with other medicalimaging procedures, contrast-enhancing fluids (often referred to ascontrast media) can be injected into the body to increase the differencein the reflected energy and thereby increase the gray scale or colorcontrast displayed in the image (that is, the image contrast) viewed bythe operator.

For ultrasonic imaging, the most common contrast media contain manysmall bubbles (sometimes referred to as microbubbles). The difference indensity of bubbles when compared to water, and thus their difference insound transmission, makes small gas bubbles excellent means forscattering ultrasound energy. Small solid particles can also serve toscatter ultrasonic energy. Such particles are typically on the order of1 to 10 microns (that is, 10⁻⁶ to 10⁻⁵ meters) in diameter. These smallparticles can pass safely through the vascular bed, and in some cases,traverse the pulmonary circulation. Contrast agents are also used fornon-vascular applications such as assessment of tubal patency ingynecological applications.

Contrast media suitable for use in ultrasound are supplied in a numberof forms. Some of these contrast media are powders to which liquid isadded just before use. The powder particles cause gas bubbles tocoalesce around them. The powder must be mixed with a liquid, and themixture must be agitated with just the right amount of vigor to get theoptimum creation of bubbles. Another type of contrast medium is suppliedin a liquid form that requires hypobaric or pressure activation. A thirdtype of contrast medium is a liquid that is agitated vigorously. Thereare no solid particles to act as nuclei, but the liquid is a mixture ofseveral liquid components that make relatively stable small bubbles. Afourth type of contrast medium uses “hard” spheres filled with a gas.These contrast media are typically supplied as a powder that is mixedwith a liquid. The goal is to suspend the spheres in the liquid withoutbreaking them. Even though such spheres have a shell that is hardcompared to a liquid, they are very small and relatively fragile. It isalso possible for the solid particles themselves to act to scatterultrasonic energy, but the acoustical properties of the solid spheresare not as different from water as those of a gas. Entities such asmicrobubbles, microspheres and solid particles suitable to enhanceultrasonic imaging contrast are referred to herein as contrastenhancement agents. For X-ray based imaging, atoms, molecules or solidparticles generally absorb X-rays at a higher rate than blood and gas orgas-filled structures generally absorb X-rays at a lower rate thanblood.

Contrast enhancement agents also enhance other modes of ultrasonicimaging. For example, when the microbubbles, microspheres or particlesare carried along in the blood stream, the reflected energy is Dopplershifted. This Doppler shift allows an estimation of the speed of bloodflow. Bubbles can also be excited so that they radiate ultrasonic energyat an harmonic of the incident ultrasonic energy. This harmonic imagingis only possible with the use of contrast medium.

After mixing/preparation as described above, the contrast medium isdrawn into a syringe or other container for injection into the patient.Typically, the fluid is injected into a peripheral vein in the arm ofthe patient, although it may be injected into other body cavities forspecific imaging procedures, for instance the intestinal tract or thefemale reproductive tract. When injected into the bloodstream, the blooddilutes and carries the contrast medium throughout the body, includingto the area of the body being imaged (that is, the region-of-interest orROI).

It is becoming more common for a microprocessor-controlled, poweredinjector to be used for injecting the contrast medium. The use of suchpowered injectors provides the benefit of maintaining a consistent flowover an extended time period, thereby providing a consistent amount ofcontrast medium in the blood stream. For ultrasound, if there are toofew contrast enhancement agent particles per unit volume in the flow,however, an insufficient image contrast may result and thereby preventan accurate diagnosis from being made. If too many contrast enhancementagent particles are present, on the other hand, excess energy isreflected, thereby resulting in blooming or saturation of the ultrasoundimage.

Thus, although a power injector can inject contrast medium at a constantflow rate (volume per unit time), there typically must be a generallyconstant number or amount of contrast enhancement agent particles pervolume of fluid injected to provide a constant image contrast. If theconcentration of particles changes, the image contrast will be degraded.There are many reasons why the number of contrast enhancement agentparticles per volume of a certain contrast medium (and thereby the imagecontrast) can vary during an injection procedure. For example, densitydifferences between the contrast enhancement agents and the fluid mediummay result in separation. Moreover, the initial mixing may not haveresulted in a homogeneous dispersion or suspension. Likewise, bubbles ormicrospheres of certain contrast media can be destroyed under conditionsexperienced in mixing, storage or delivery of the contrast media.Additionally, a number of conditions or parameters of the injectionfluid other than the concentration of the contrast enhancing agentstherein can he changed. For example, the injection flow rate, the volumeof medium injected and the injection pressure can be changed in acontinuous or discontinuous manner. In addition most newer ultrasoundenhancement agents and most existing X-ray enhancement agents passthrough the pulmonary circulation and can circulate more than oncethrough the body, so that they build up in the patient's blood pool. Theextent to which this happens differs from patient to patient. This isanother reason for having feedback from the imaging system to theinjector to control the injection.

Referring to FIG. 1, injection and imaging system 10 delivers a fluidmedium including a suspension of microbubbles 30 suspended in a fluidcarrier to patient 20. Certain components of system 10 are discussed indetail in U.S. Pat. No. 6,317,623, the disclosure of which isincorporated herein by reference.

In the embodiment of FIG. 1, a syringe or pressurizing vessel 40 drivesfluid through a fluid path element 50. Fluid path element 50 may passthrough a bubble or contrast enhancement agent concentration regulator60 that can affect the enhancement properties of the agent by, forexample, selectively destroying microbubbles 30. Bubbles 30 may bedestroyed, for example, by insonating the fluid with ultrasound energy,generating local temperature or pressure changes in the media or by sometypes of mechanical agitation.

The ability to destroy microbubbles 30 in the fluid path may enablebetter control of the imaging procedure. Because mechanical resonance ofa bubble wall is a function of bubble size, for example, it may bepossible with the proper power and frequency settings to selectivelydecrease the concentration of bubbles of a certain size. Such selectivedestruction allows control of the bubble distribution. Microbubbles 30can also be destroyed in the fluid path as part of a strategy to controlcontrast agent concentration. It is also possible to reduce the amountof contrast enhancing agent flowing into the patient simply by reducingthe flow rate of the media.

Fluid path 50 continues through a concentration sensor 70 suitable tomeasure the concentration of microbubble 30 in the fluid medium. Suchsensors are discussed in detail in U.S. application Ser. No. 09/267,238referred to above.

Fluid path 50 then continues on through a patient interface 80 to aninjection site on patient 20. The output of sensor 70 preferably passesto a control/communication interface 90 which may, for example, be incommunicative connection with or combined with a processor unit 92suitable to, among other things, process signals corresponding to, forexample, concentration data from sensor 70 and to send control signalsbased upon such incoming data to other components of system 10. Acontrol signal corresponding to the concentration data may be sent fromprocessing unit 92 via interface 90 to any number of devices in deliverysystem 10 including, for example, an imaging unit such as an ultrasoundscanner 100. The control signal can be used, for example, to adjust theimage (for example, by increasing or decreasing the power in the signalsent into the patient, the time during which the energy is applied tothe patient, the gain or other machine settings of the amplifier whichreceives the signal from the patient, or the speed at which the energyis scanned across the patient), to provide concentration information aspart of documentation and/or to assist with diagnosis during the imagingprocedure. Information can also preferably be sent from imaging unit 100to processing unit 92 to, for example, control other devices such as,for example, an agitation/preparation mechanism 110 (including, forexample, a mechanical stirrer 114), a powered injection control unit 120and/or a concentration regulator 60.

Agitation/preparation mechanisms suitable for use in the presentinvention are disclosed in U.S. application Ser. No. 09/267,237,entitled AGITATION DEVICES AND DISPENSING SYSTEMS INCORPORATING SUCHAGITATION DEVICES, filed on Mar. 12, 1999, the disclosure of which isincorporated herein by reference. In that regard, several commercialagents now available require some kind of agitation or mixing forpreparation. These include, but are not limited to: ALBUNEX and OPTISONavailable from Molecular Biosystems, Inc. of San Diego, Calif.; andLEVOVIST available from Schering AG of Berlin, Germany.

The data communication and control devices and systems of the presentinvention can be used during initial preparation of the medium, duringan injection procedure to effect a desired result, or after an injectionto review performance and status. In that regard, certain contrastmedia, such as LEVOVIST, are known to precipitate or separate over timein some of the higher concentrations (for example, 400 mg/ml).Concentration measurement can be used to detect such separation andrestart or increase agitation to help reduce precipitation effects.

Concentration sensor 70 can be located anywhere on the fluid deliverypath from syringe or pressurizing vessel 40 to patient interface 80. Ifconcentration sensor 70 is located near the patient injection site atthe end of fluid path 50, one can better account for microbubbledegradation effects from shear rate, temperature and other deliveryeffects. Since sensor 70 preferably does not require direct contact withthe contrast enhancement agent, a coupling piece can be made as adisposable part of a tubing set for convenience in attaching sensor 70and or concentration regulator 60 and to maintain sterility with patientinterface 80. The sensing region is preferably a known volume or area ofthe contrast media surface located on fluid path 50.

Other sensors or sensing equipment can be in communicative connectionwith interface 90. For example, a sensor or sensors (not shown) can bepart of system 10 to provide direct measurements of the concentration ofthe fluid medium and/or the contrast enhancement agents within thepatient's body. Another example is bar code readers which inputinformation about the contrast media including but not limited tovolume, concentration, manufacture date, manufacturer. Moreover,interface 90 can be in unidirectional or bi-directional communicativeconnection with a sensing and/or measuring device 130 that provides dataon one or more physiological conditions of the patient. For example,device 130 can be a heart rate or blood pressure monitor.

Previous injector systems have contained an electrocardiograph (ECG)that is used to set start of injection trigger points synchronized withvarious portions of the cardiac cycle. In the present invention, otherequipment such as heart rate or blood pressure monitors may be used toprovide patient physiological data to control the injection or imagingprocess, especially during an injection. For example, during ultrasoundcardiac stress echo imaging, vasodilator and vasoconstrictor drugs areadministered to increase and decrease cardiac output load. Connectedsensors for monitoring heart rate and blood pressure may be used toinitiate, terminate or adjust the injection process when theseparameters reach certain levels. The output from these sensors can alsobe used to adjust other aspects of the imaging process, such as scannersettings. Unlike prior systems, the present invention allows isolation,digital communication, bi-directional or two-way communication and/orcommunication with an imaging system.

In addition, it may be useful to control the delivery of sometherapeutic or diagnostic agents during contrast imaging based ondisplay or signal information from the imager as a result of the imagingprocedure. For example, during ultrasound cardiac stress echoprocedures, a drug, Dobutamine, which is a cardiotonic or cardiovascularstressor agent, is often used to increase cardiac stress so that cardiacparameters can be measured and quantified. (Dobutamine is a syntheticderivative of dopamine, characterized by prominent inotropic but weakchronotropic and arrhythmogenic properties.) An injection system may beused to control the delivery of the stressor drug during an enhancedprocedure based on visual information from the imager, such as peak flowrate in a vessel from a Doppler image, the intensity of a perfusedtissue region, vessel geometry measurements, or heart chamber geometrymeasurements during various portions of the cardiac cycle. The deliveryof such a drug can also be controlled by the signal at the imager beforeit is generated into a display, for example, using acousticintensitometry. This concept can be extended to other imaging modalitiesand to the administration of other therapeutic or diagnostic drugs orsubstances.

Interface 90 can also be in communicative connection with an informationstorage and processing unit 140 of a hospital or other care-givingorganization to, for example, receive information regarding a patient toassist in control of injector controller 120 or to transmit informationregarding an imaging procedure from any other device of imaging system10 for storage and/or processing by hospital processing unit 140.

Interface 90 can also be in communicative connection with an operatorinterface 150 so that the operator(s) of imaging system 10 may receiveinformation about the patient and the components of imaging system.Data, such as control parameters or algorithms, can also preferably besent from user interface 150 to interface 90. It may be preferable tophysically partition the operator interface so that some simpleinjection related information such as volume remaining is available nearthe syringe. It is preferable that all injection and scanninginformation be available so that the operator can quickly accessrelevant information during the imaging procedure. Currently, ultrasonicimagers use a display that combines the image and informative textaround the image. Two different displays may be used for cost reasons orfor ease of use. Information that may be displayed for operatorconsideration includes but is not limited to: time since the fluid wasinitially prepared, information such as brand or initial concentrationread from contrast media packaging, initial injection parameters for asingle or multilevel injection, and the status of the injectorcontroller (for instance, disarmed, armed, injecting).

Operator interface 150 also preferably incorporates operator inputdevices including but not limited to keys, a track ball, a mouse, ajoystick, a voice recognition system, and/or a touch panel as known inthe art. These input devices allow the operator to make initial settingsor to input information about the patient or the imaging procedure whichthe processor 92, the controller 120, or the imager 100 can use toprepare for or conduct the imaging procedure. The operator interfacealso enables the user to ready the injector for injection (arm theinjector) or to disarm. It can also allow the operator to confirm thatthe proper procedure has been followed in eliminating gross air from thefluid path elements. The operator interface allows the operator todetermine information used from or sent to other components such as butnot limited to optional use of patient information such as patientphysiologic parameters through external device interface 130 or outputof selected information to the hospital processor 140.

An embodiment of interface 90 will be discussed in the context ofcommunication with injector control unit 120. FIG. 2, for example,illustrates an embodiment of interface 90 in communicative connectionwith injector control unit 120 via cabling 94. Interface 90 canpreferably be connected to other devices of system 10 via any wired orwireless media for carrying the information (for example, RS-232,parallel, RS-485, LAN, etc.) using any unidirectional, pairedunidirectional, or bi-directional networking or communication protocol(for example, TCP/IP, IPX/SPX, etc.) as preferably selected by anoperator. Refer to Table 3 for a summary of some of the possiblecommunication connections and protocols.

Data communication and control can be effected with use of interface 90in part, for example, through definition of various operational statesof the components of system 10. For example, a ready/armed state can bedefined as the state of injector controller 120 prior to performing aninjection. This state may be set upon completion of specific diagnosticfunctions and indicates that injector controller 120 is ready andawaiting a signal to begin an injection. An idle/disarmed state candefine an idle state of injector controller 120 during which programmingoperations are performed. Preferably, the idle/disarmed state is thepower-up default state and the state that injector controller 120returns to after performing any injection sequence. There can be anarmed multi-inject state, which allows a series of injections beforereturning to the idle state. Injector controller 120 is preferablyalways in the idle/disarmed state when connecting to or disconnectingfrom patient 20. A hold state of injector controller 120 is preferablyentered after the operator or another system component has temporarilysuspended the injection. Injector controller 120 may, for example,remain in this state for a period of time before disarming whileawaiting a signal to resume the injection. An injecting state definesthe state of injector controller 120 while performing an injection. Thisstate is entered typically only from a ready/armed state.

A set of injection conditions or parameters is preferably entered intothe system (for example, by an operator via operator interface 150) todefine certain criteria of how an injection is to be performed. Theseconditions or parameters can include, for example, volume, flow rate,number of phases, fluid source or type (where A and B are two types offluid), and whether there is a scan delay or injection delay associatedwith the programmed injection (that is, delivery of fluid according to aprogrammed injection profile).

Operational and state parameters are preferably provided betweencomponents of system 10 via interface 90 (for example, between injectorcontroller 120 and imaging unit 100) at an update rate sufficient toallow effective real-time control of the imaging procedure (for example,to allow imaging unit 100 to produce a clear image of the injectionprocess). For peripheral venous injections control does not need to beinstantaneous because there is a variable delay from the time the fluidis injected into the patient to the time it reaches the imaging site, aswell as a delay from when the fluid passes the concentration sensor 70and the time it flows into the patient. A second function of theinterface 90 is to allow control parameters to be passed betweencomponents of imaging system 10.

Typical operating parameters include, for example, programmed infusionrate, programmed bolus bate, programmed bolus volume, flow rate, totalinjected volume, volume remaining, bolus ready, infusion ready, bolusrunning, infusion running, low volume, infusion pending, bolus complete,flow profile rise/fall rates, injection aborted/canceled, error codes aswell as internal diagnostic information and injector machine state.Typical control parameters may include, for example: hold injection,start injection, start scan, stop injection, stop scan, gated operations(Start/Stop) in relation to some patient parameter such as breathing orECG, reset injector, programming commands, preparation commands, loadingcommands, or any other injector functions that could be activatednormally by the user or by other means.

The following is an example of a data communication protocol for usewith interface 90. Imaging unit 100 may, for example, include anultrasonic scanner that operates in conjunction with an injection system(including injector controller 120 and pressurizing syringe 40) toinject a contrast agent to enhance a targeted area of concern or regionof interest of patient 20. Injector controller 120 and imaging unit 100may be interconnected via interface 90 (for example, including an RS-232serial interface) using standard control lines Request to Send (RTS) andClear to Send (CTS) to manage the data flow. A simple protocol may bedefined wherein injector controller 120 provides all of its operatingparameters via interface 90 periodically, for example every 500milliseconds, as long as the CTS line from imaging unit 100 is set(injector controller 120 signals its readiness to imaging unit 100 bysetting RTS). After receipt of a message imaging unit 100 may simplyacknowledge data packets received from injector controller 120. Imagingunit 100 can also send control commands or in a separate message asnecessary to control the injection/imaging process. Injector controller120 may simply acknowledge command packets received from imaging unit100 and may perform the requested action if it is safe to do so.

In one sequence of events, an operator sets up injector controller 120by following all required procedures to the point where injectorcontroller 120 is in an ‘Armed’ or ‘Ready’ state. At this point theoperator can concentrate fully on operation of imaging unit 100. Whenready, the operator can use a command from the imaging unit 100 toinjector controller 120 (via interface 90) to begin a programmedinjection. During the programmed injection and scan, the injectorcontroller 120 is preferably providing a rapid update of its process andstatus. At any time, the operator preferably can abort the injection(from either the injector or imaging system or take over active control,for example, adjust the flow rate.

Interface 90 thus facilitates an integrated control feature betweendevices of injection and imaging system 10, permitting enhancement ofdiagnostic information. System 10 gives an operator the provisions tomanage many or all of the components of system 10 (and, thereby, allfacets of the injection and imaging procedure) from the most convenientplace. Indeed, a single operator can easily perform a contrast-enhancedscan using the procedural ease afforded by the integrated approach ofsystem 10. Any number of quantification algorithms that expand thediagnostic capability of the system can utilize the information providedover interface 90 to maximize the quality and diagnostic utility of theimages.

For example, there are numerous applications for an ultrasound injectorwith a bi-directional data and control communications interface 90,especially in the areas of closed loop control of injector controller120 based on an acquired signal or image. Such applications may bedivided broadly into two classes, diagnostic and therapeutic.

As a diagnostic application, a communication interface 90 betweeninjector controller 120 and scanner 100 can be used to detect lesionsand tissue characteristics through differences in tissue vascularconcentration or perfusion. The technique is useful as a method fortumor detection and identification. Closed loop control can, forexample, be used to provide relatively constant enhancement of tissuewithin a region of interest to help identify tumors in those areas.

Video density, video intensity, acoustic intensity or acoustic Dopplerintensity information (that is, raw acoustical data) from scanner 100can be used to control the injection profile (for example, as a way tocontrol injected enhancement agent concentration) to provide the desiredtime response and level of enhancement. An algorithm in processor unit92 or control unit 120 can accommodate for delays between a change in aninjection parameter such as flow rate and the appearance of the changeat the imaging site. Because tumors are often hyper-vascular orhypo-vascular relative to surrounding normal tissue, tumors can beidentified by differences in enhancement level or enhancement levelchanges over time. A similar technique can be used to observe andquantify tissue perfusion during contrast enhanced myocardialechocardiography or other perfusion studies.

Closed loop control can be used to control the concentration of theenhancement agent in a region of tissue. The level of enhancementrequired, the level of enhancement or the time response of enhancementincrease or decay can be used to observe tissue perfusion, since theenhancement agent will be present in the small vessels that perfuse theregion of interest. This technique can also be combined with the use ofvasoconstrictor/vasodilator drugs, physical stress, or other means toinduce cardiovascular stress to make changes in perfusion morepronounced or detectable.

Another diagnostic application for interface 90 is to control parameterssuch as concentration, flow rate or time or timing of injection based ondata of a physiologic parameter, such as heart rate, provided byexternal device 130. An example of a procedure is closed loop drugdelivery of cardiac stress agents while imaging. In this technique, astressor agent is injected and controlled based on heart rate. Once atarget heart rate is achieved it may be useful to synchronize andcontrol the level of injected enhancement agent, or to provide bolusinjection control for diagnostic purposes. In that regard, informationfrom imaging unit 100 can be used to control the delivery of theenhancement agent. Interface 90 can also be used to terminate aninjection if a certain level of enhancement has not been reached withina certain time period, preventing waste of the imaging agent and savingprocedure time. Or it can simply warn the operator that conditions areoutside some optimal window and let the operator take appropriateactions. This technique can be generalized to injection communicationand control based on information from other external equipment orpatient physiological parameters.

Information from the concentration sensor 70 can be used to affect theinjection parameters, or it can simply be communicated via interface 90to the operator interface 150 so that the operator has access to theconcentration information during the imaging procedure. The operator isthe one who takes action to adjust the injection, stop the procedure ortake other appropriate action. This has a potential advantage inachieving quicker regulatory approval for the manufacture and sale ofthe device. This allows the operator to make the decision versus thesystem taking action automatically, which may require more validationeffort. Also data from concentration sensor 70 could be transmitted tothe imager 100 directly or after processing in the processor 92 so thatparameters of the imaging unit mentioned elsewhere can be adjusted toachieve a satisfactory diagnostic image in spite of changes inconcentration of the contrast-enhancing agent.

There are also many therapeutic and other applications of imaging system10. For example, enhancement agents may be used as a means forsite-specific imaging and for activated drug or gene therapy delivery.For example, ImaRx of Tucson, Ariz. has an agent under development,MRX-408, based on their previous agent DMP-115 (DEFINITY), a multilipidencapsulated perfluoropropane and air echo enhancing agent thatincorporates site specific binding for the detection of thrombus. Someultrasound and x-ray imaging agents are being developed that releasedrugs or are “activated” when insonated or bombarded with x-ray energy.Image video intensity, acoustic intensity, acoustic Doppler intensity orother image information can be used with these agents to track andcontrol the concentration of an agent within a region over time. Coupledwith injector controller 120 and interface 90 for injection control, thedelivered agent concentration or total agent dose can be controlled formaximum therapeutic effect and to prevent overdose.

For example, a certain drug delivery imaging agent can be injected undercontrol of imaging system 10 so that the observed enhancement isstabilized at a target level for a certain period of time. During thistime, the drug of the agent can be activated within the region ofinterest using, for example, ultrasound or x-ray energy. Once the timeperiod of sufficient enhancement expires, the injection can beterminated by control from imaging unit 100. Information on theinjection delivery history (e.g., the flow rate profile) and total dose(e.g., total volume delivered) can be sent to the imaging unit 100 orhospital processing unit 140 for record keeping and documentationpurposes. Other methods, such as using the time integral of image pixelintensity, can be used to measure and control the total delivered doseof the agent. With microbubble-based delivery of active substances inultrasound, information from the imaging unit 100 can also be used tomake sure that all of the agent within a certain region has beencompletely activated before ending the injection, maximizing thedelivered dose within the region of interest. Other agents may becomeavailable in the future that are activated by electromagnetic(especially optical), magnetic, or nuclear radiation. All suchactivation energy sources are suitable for use in the present invention.

Another application of real-time data and control interface 90 is forcontrol of pulsed flow for therapeutic applications. In pulsed flowthrombolysis, for example, high flow rate but short duration bolusinjections are used to both mechanically disrupt or ablate andchemically dissolve thrombi in vessels. Image information regarding theprogress of clot dissolution can be used to communicate changes to theinjection system flow rate, agent concentration, pulse duration andother fluid delivery parameters. While not shown in the figure, aduplicate injector with duplicates to syringe 40 and control unit 120could be injecting the therapeutic agent into the patient andcooperating through interface 90 with simultaneous or alternatinginjections of therapeutic agent, flushing agent (such as saline) andimaging agent. In some applications it can be advantageous to controlthe injection of three (3) or more fluids by using multiple injectionmechanisms in communications with each other through interface 90.

In certain therapeutic injections, it is desirable to synchronize thedelivery of short boli of therapeutic fluid with that portion of thecardiac cycle that ensures turbulent mixing with blood. Withoutturbulent mixing, these toxic fluids can be entrained in streamlines oflaminar flow, which carry the fluid beyond the area of intendedapplication. In this case, the fluid is typically introduced by aperipheral arterial access. A precise volume of fluid must be injectedby breaking it up into small volume packets timed to the cardiac cycle.A communications link to injector controller 120 can be used to controlthe timing of fluid delivery in this application.

FIG. 3 illustrates an example of a block diagram that partitions thefunctions described above between separate injection subsystems andimaging subsystems. This embodiment may, for example, accommodate asituation in which the various subsystems are separately manufactured bythe same or different manufacturers and/or a situation in which thesubsystems require separate regulatory approvals.

In FIG. 3, the unpartitioned components retain the same numbers as inFIG. 1. For those that are partitioned between the two subsystems, thosepartitioned into injector subsystem 15 a of the system generally includea suffix “a” and those partitioned into imager subsystem 15 b generallyinclude a suffix “b.” Component 90 c is the interface connection betweenthe two subsystems.

Injector subsystem 15 a includes generally those elements for thecontrol of the fluid flow. Injector subsystem 15 a includes, forexample, concentration sensor 70 and external device 130. Injectorprocessor unit 92 a takes and receives information from an injectoroperator interface 150 a and the other components through injectorinterface 90 a.

Imager subsystem 15 b includes generally elements for the control of theimaging energy and the creation of an image or measurement as discussedabove. Imager subsystem 15 b includes, for example, a processor unit 92b that takes and receives information from an imager operator interface150 b and the other components through imager interface 90 b.

It is possible for the subsystem components to be partitioned in otherways. For instance, concentration sensor 70 might be part of the imagersubsystem 15 b. The same applies to external device 130. FIG. 3 showsboth subsystems having separate communications to the hospitalinformation system 140. It may be that only one of the subsystemscommunicates with the hospital interface 140. Other partitioning ispossible as well.

All communications between the two subsystems preferably take placethrough subsystem interface 90 c. A benefit of this partitioning is theisolation of the need for the most stringent error control andverification to the operation of subsystem interface 90 c.Communications within each subsystem can be more easily tested as aself-contained unit.

Present imaging systems use a simple relay closure as an interfacebetween subsystems so that one subsystem can tell the other to start apreprogrammed function. By having a subsystem interface 90 c transmitinformation, many of the above listed benefits are possible.

In addition to timing information communicated via relay closures byprior systems, the data transmission enabled by the present inventionincludes, for example, information sent between devices regardingoperating parameters, operator input, device status information, andcontrol sequencing. In addition, data transferred from one device toanother device can be used to enable active control of the receivingdevice from that data. For example, during the injecting state, datatransmission from an ultrasound scanner can be sent to an injector toenable active control of the injection flow rate based on the datareceived.

The discussion below provides a list of example capabilities possiblewith interface 90 c between the subsystems of the present invention.Many of these have also been discussed above. Injector subsystem 15 acan send information about its state or its programs to imagingsubsystem 15 b such as, but not restricted to:

-   -   Contrast enhancing fluid type or volume, read by bar code or        operator input    -   Contrast enhancing fluid concentration    -   Time since mixing of the contrast enhancing fluid    -   Time since last injection    -   Time since start of current injection    -   Time of last servicing    -   Injector system unique identification number or code    -   Injector hardware or software configuration (version number)    -   Status of agent agitation, for instance, mixing or ready    -   Current Selected Infuse Rate    -   Current Selected Bolus Rate    -   Current Selected Bolus Volume    -   Current injection Phase    -   Actual Flow Rate    -   Actual Volume Delivered Total Injected Volume    -   Volume Remaining    -   Bolus Ready    -   Bolus Low Volume    -   Bolus Running    -   Bolus Complete    -   Infuse Ready    -   Infuse Running    -   Infuse Pending    -   Injection Stopped or Canceled    -   Injector Error Detected and Type

Information such as set forth above can be used by imager subsystem 15 bto adjust its operation to optimize the image acquisition process asdescribed above. It can also be displayed on the imager subsystemoperator interface so that it is convenient for the operator to assessthe injector subsystem's functioning. It may be that imager subsystem 15b cannot automatically adjust its operation based upon the transmittedinformation, but that the operator has to make an adjustment. Theinformation could be displayed at the imager to allow the operator toview the information before making adjustments. This may be forregulatory approval or to simplify subsystem design verification.

Information can also be transmitted from imager subsystem 15 b toinjector subsystem 15 a. This information may be used to adjust theinjector subsystem operation as mentioned above, or it may simply bedisplayed so the operator at the injector user interface 150 a can beinformed about key imager subsystem information. A basic benefit is theability to start and stop the injection from imager operator interface150 b. A much more sophisticated capability is to be able to programall. injector functions from the imager subsystem operator interface 150b as if the operator were at injector subsystem operator interface 150a. An example of a middle ground is if injector subsystem 15 acommunicates possible preprogramming sequences to imager subsystem 15 b,and the operator at imager operator interface 150 b chooses among thesequences.

Another benefit of data communication between subsystems is the abilityfor imager subsystem 15 b or the operator at imager subsystem operatorinterface 150 b to determine that an image or measurement was notsufficient and command the injector to repeat the injections or toperform a different injection. A planned example of this is what isoften termed a test injection. After an injection is made and a seriesof images or measurements are acquired, scanner/imager processor unit 92b or injector processor unit 92 a can determine from the informationgathered the injection parameters, including timing, that are mostlikely to create the desired enhancement in the final image ormeasurement.

Given the criticality of the information being transmitted between thetwo subsystems, it is desirable that there be significant safeguards toprevent error or problems. In a preferred embodiment, the electricalsignals of the two subsystems are not electrically connected to eachother, which can be accomplished in many ways. Optical isolators,isolation transformers and capacitance based isolators commonly usedcomponents for providing electrical isolation. Other means of isolationare by the use of transmitted or broadcast electromagnetic or ultrasonicenergy for the transmission means.

It is also preferable that each subsystem be able to operate even ifinterface 90 c is not operating. This result can be accomplished withinthe programming of each subsystem processor unit. If the operator triesto use a function that requires communications between subsystems, andcommunications are not available or in an unknown state, the operator ispreferably either informed of that condition, or an attempt tocommunicate is made and the operator is informed of the results of thatattempt.

It is also preferable to structure data transmission so that errors areavoided or tolerated. The discussion below provides an example procedureto provide error detection and tolerance. The example discussesinformation transmission from injector subsystem 15 a to imagersubsystem 15 b with acknowledgement of proper receipt by imagersubsystem 15 b being sent to injector subsystem 15 a, but the samemethodology can be readily applied with the respective roles reversed totransmit information in the other direction. The use of two separatetransmission channels can be used as discussed below. A singletransmission channel can also be used.

EXAMPLE

In one embodiment, injector subsystem 15 a periodically transmits statusinformation through subsystem interface 90 c to imager subsystem 15 b,which preferably only has to acknowledge the successful (orunsuccessful) data reception. In this embodiment, imager subsystem 15 bdoes not request data from injector subsystem 15 a or send data otherthan acknowledgements to injector subsystem 15 a. A message based flowcontrol mechanism is preferably used to regulate the data flow frominjector subsystem 15 a.

In this embodiment, only two different messages are preferably sent frominjector subsystem 15 a to imager subsystem 15 b. The injector subsysteminterface status message preferably contains the interface softwareversion number and indicates if injector status information isavailable, and the injector status message preferably contains, forexample, injection parameter values and volume information. The injectorsubsystem interface status message is preferably transmitted whenconnection is established or resumed, which is determined by the statusof the handshake lines. It is preferably sent approximately every 500milliseconds (not including retries) as long as injector statusinformation is not yet or no longer available. If injector statusinformation is available and the injector subsystem interface statusmessage has been acknowledged, the injector status message is preferablytransmitted approximately every 500 milliseconds (not includingretries).

The following discussion provides a detailed description of thecommunication protocol and the format of the two messages discussedabove.

Data Exchange Mode

Communication may, for example, be serial, asynchronous and full duplexat 19200 Baud with flow control using RTS/CTS. Each data frame sentbetween the two subsystems preferably comprises ten bits: one start bit(logic 0), eight data bits (LSB first, no parity), and one stop bit(logic 1). The start and stop bits preferably have the same width asdata bits. The electrical interface is preferably designed to becompatible with the EIA RS-232.V28 standard.

Message Format

Messages sent from injector subsystem 15 a to imager subsystem 15 bpreferably have the format set forth in Table 1:

TABLE 1 Sequence Message Message STX Number Length Data CRC ETX 1 1 (2)1 (2) up to 48 (96) 1 (2) 1 byte byte byte byte byte byteNumbers in parenthesis in Table 1 represent the actual size duringtransmission after data folding has been performed. Data folding isdiscussed below.STX

The STX (start of text) transmit) transmit) transmit) characterindicates the beginning of a message. The one byte hexadecimal code forSTX is, for example, 0x02.

Sequence Number

A one-byte sequence number is preferably used to enable the receivingsystem to detect a retransmitted message. The sequence number isnecessary for the case that a message is successfully transmitted andreceived but the receiver's acknowledge becomes corrupted. Thetransmitting system preferably retransmits the message after a responsetime-out has occurred. As the receiver already received the messagesuccessfully the first time, it can identify the message as a duplicateby checking the sequence number against the sequence number of the lastreceived message. The receiver preferably acknowledges and then discardsthe duplicate message. The receiver, therefore, preferably maintains areceive sequence number which is set to the sequence number of areceived message after it has been validated. The transmitter alsopreferably maintains a transmit sequence number which represents thesequence number of the last message for which a positive acknowledge wasreceived. An example of internal transmit and receive sequence numberingfor a message transmission and the receiver's response is illustrated inFIG. 4.

Message Length

The one byte Message Length field specifies the size of the followingMessage Data field in bytes. The Message Length value range is, forexample, 1 to 48.

Message Data

This portion of the message is the data portion of the message. If amessage contains data items comprising multiple bytes, the byte order ispreferably little endian (least significant byte first). Examples ofsupported messages and associated message format are discussed infurther detail below.

CRC

An eight-bit CRC is preferably used to secure the data to betransmitted. It enables the receiving system to detect message datacorruption. The CRC covers the Sequence Number, Message Length, andMessage Data fields before folding. An example of a polynomial used tocalculate the CRC is: x⁸+x⁴+x²+x+1.

ETX

The ETX (end of text) character indicates the end of a message. The onebyte hexadecimal code for ETX is, for example, 0x03.

Message Acknowledge

As mentioned above, the receiving system preferably acknowledges eachreceived message by sending a single control character. The transmittingsystem preferably does not transmit a new message until the lasttransmitted message has been acknowledged or a response time-out hasoccurred. An acknowledge can be positive (ACK), indicating successfulmessage reception and CRC validation, or negative (NAK), indicating aninvalid CRC or a receive time-out. The injector preferably retransmits amessage until it receives a positive acknowledge. If a status messagehas to be retransmitted and updated status information is available, anew message with the updated status is preferably sent instead. The onebyte hexadecimal code for an ACK is, for example, 0x06. A NAK isrepresented as hexadecimal 0x15.

Data Folding

To avoid data escaping, all bytes between the STX and ETX controlcharacters are preferably ‘folded’ to guarantee that their values fallwithin the printable ASCII character range (0x20 to 0xE7) and do notoverlap with control characters. This result is achieved by splittingeach byte into two nibbles and adding a fixed offset to each nibble. Theoffset to be used is preferably 0x30. Folding the data between the STXand ETX, therefore, doubles the size of a message. An example messageand the folded data to be transmitted are given below in Table 2:

TABLE 2 Original Message Folded Message STX 0x02 0x02 Sequence 0x100x30, 0x31 Number Message Length 0x02 0x32, 0x30 Message Data 0x45, 0x670x35, 0x34, 0x37, 0x36 CRC 0xB6 0x36, 0x3B ETX 0x03 0x03Handshaking

Two hardware signals (CTS and RTS) may be used to implement a messagebased flow control as described above.The signals may also be used to detect connection between injectorsubsystem 15 a and imager subsystem 15 b. FIG. 5 illustrates the signalsand how they are connected.

Connection Establishment

The injector preferably activates RTS once it is ready to transmit datato imager subsystem 15 b. The RTS signal preferably stays active as longas injector subsystem 15 a is powered up and operating normally. Initialconnection is preferably established when injector subsystem 15 a hasactivated its RTS output and detects its CTS input as active for thefirst time. Connection is preferably resumed when injector subsystem 15a detects its CTS input as active after it had been deactivated. Imagersubsystem 15 b can activate its RTS output (the injector's CTS input) atany time; it is not required to wait for injector subsystem 15 a toactivate its RTS output first.

Flow Control

Injector subsystem 15 a preferably transmits the injector subsysteminterface status message when connection is initially detected orresumed. Once injector status information is available and the injectorsubsystem interface status message has been acknowledged (ACK), injectorsubsystem 15 a preferably transmits the injector status message aboutevery 500 milliseconds, not including retransmits. As long as imagersubsystem 15 b does not deactivate its RTS signal, injector subsystem 15a preferably continues its periodic transmission. If imager subsystem 15b deactivates its RTS output, injector subsystem 15 a preferablyfinishes the current message transmission. It then waits for imagersubsystem 15 b to activate its RTS signal again. When the imagersubsystem's RTS output is active again, injector subsystem 15 apreferably restarts transmission with an injector subsystem interfacestatus message. FIG. 6 illustrates a flow control example: (INJECTORSUBSYSTEM interface status messages are indicated by a solid border).

Time-outs

The requirement that each successfully received message be acknowledgedby the receiver, has the side effect that the transmitter canpotentially wait forever for an acknowledge (ACK/NAK). Another possibleerror condition is that the transmitter aborts the transmission beforethe ETX character is sent. A set of time-outs are preferably used toallow the transmitting and receiving systems to recover from thesesituations.

A time-out duration may, for example, be based on the followingcalculations: At a baud rate of 19200 it takes about 52 microseconds totransfer one data bit. One data byte (a 10 bit frame) can, therefore, betransmitted in about 520 microseconds. Assuming no delay between bytes,transmission of a maximum length message (104 bytes, folded) takesapproximately 54.1 milliseconds. The required one-byte response from thereceiver adds another 520 microseconds, not taking any validation andprocessing of the received message into account.

Transmit Time-out:

A message transmission time-out may be used to account for situations inwhich the transmission of a message never completes or takes too longbecause of an internal transmitter problem. If a transmission time-outis not incorporated, the injector could possibly wait forever for thecompletion of a message transmission, which would block the transmissionof all subsequent messages. As previously discussed, a maximum lengthmessage can be transmitted in a minimum of 54.1 milliseconds. Allowingsome delay between bytes because of processing overhead, the transmittime-out may, for example, be set to 60 milliseconds. The transmittime-out period begins with the STX character being transmitted.

Receive Time-out:

A message receive time-out may be used to account for situations inwhich the reception of a message never completes (e.g. ETX missing) ortakes too long. If a receive time-out is not incorporated into thedesign the imager subsystem could possibly wait forever for thereception of a message to complete which would block the reception ofall subsequent messages. Since the timing associated with the receptionof a message is dictated by the transmitter, the same value as for thetransmit time-out (60 milliseconds) may be used. The receive time-outperiod begins when the STX character is received.

Response Time-out:

A message response time-out may be used to account for situations inwhich imager subsystem 15 b does not acknowledge or takes too long toacknowledge a received message. Even though imager subsystem 15 b doesnot send any messages in this embodiment and an acknowledge couldtherefore be expected after a few milliseconds, the response time-out isalso preferably set to 60 milliseconds. The response time-out periodpreferably begins when the ETX character is transmitted.

The section below provides a brief summary of the handling of a numberof error situations by the present communication interface system.

Error Handling

Injector Subsystem

-   Transmission Time-out: The time to transmit an entire message    exceeded the transmission time-out period. This error indicates an    internal problem of the injector transmitter. The injector will    deactivate its RTS signal, indicating that no further messages will    be sent to the imager subsystem. RTS will remain deactivated until    power is cycled off/on and the injector is ready to transmit data    again.-   Response Time-out: The imager subsystem did not respond to a message    within the response time-out period. The injector will retransmit    the last message unless updated status information is available    which would be transmitted instead of the last message.-   NAK Received: The imager subsystem did not properly receive a    message (CRC mismatch, receive time-out). The injector will    retransmit the last message unless updated status information is    available which would be transmitted instead of the last message.    Imager Subsystem-   Receive Time-out: The time that it took to receive a message    exceeded the receive time-out period. The imager subsystem will send    a NAK to request a retransmit of the message.-   STX Character Missing: Other data are received when waiting for an    STX character. The imager subsystem will discard all characters    until an STX is received. If the injector was trying to send a    message, a response time-out will occur and the message will be sent    again.-   CRC Mismatch: The CRC calculated from the received data did not    match the received CRC value. The imager subsystem will send a NAK    to the injector after the receive time-out period has expired.-   Duplicate Message Number: The received message number was equal to    the last message number received. The imager subsystem will send an    acknowledge and disregard the retransmitted message.-   Dropped Data Bytes: During reception of a message one or more data    bytes were lost. This error will most likely result in a CRC    mismatch. The imager subsystem will send a NAK to the injector after    the receive time-out period has expired.    Message Data Format

The Message Data portion of a message as discussed above may have theformat set forth in Table 3 below.

TABLE 3 ID ID specific data (1 byte) (up to 47 bytes)Supported IDs

Examples of supported messages and associated data for external deviceinterface status and injector status are provided in Tables 4 and 5,respectively. Binary data of word size are transmitted in little endianbyte order. FIG. 7 illustrates a state transition diagram of the receiveprocessing to be performed by an external device (for example, imagersubsystem 15 b) communicating with injector subsystem 15 a.

TABLE 4 Encod- Data Value Field ing Type Range Description ID BinaryByte 0xF5 Data 7 Injector Binary Bit 7 0 or 1 The bit is 1 when injectorStatus status information is Data available for transmission. AvailableReserved N/A Bit 6- N/A 0 SW Version ASCII Char ‘1.0’ [4] to ‘99.9’Reserved N/A Byte N/A [2]

TABLE 5 Encod- Data Value Field ing Type Range Description ID BinaryByte 0xFA Data Programmed Binary Word 0 to The value is given in tenthsInfusion 290 ml/min. The actual range Rate therefore is 0.0 to 29 ml/minResolution: 0.5 ml/min between 0.0 and 10, 1 ml/ min between 10 and 29Programmed Binary Word 0 to The value is given in tenths Bolus Rate 30ml/s. The actual range therefore is 0.0 to 3.0 ml/s. Resolution: 1.0ml/s Programmed Binary Word 0 to The value is given in ml. Bolus 30Resolution: 1 ml Volume Flow Rate Binary Word 0 to The value representsa non- 1800 cumulative running average while an injection is inprogress. It will be 0 before and after an injection. The value is givenin tenths ml/min. The actual range therefore is 0.0 to 180 ml/min.During a bolus, the external device should convert the received flowrate value to units of ml/s. Total Binary Word 0 to The value is givenin tenths Injected 9990 ml. The actual range therefore Volume is 0.0 to999 ml. Resolution: 0.5 ml between 0.0 and 100, 1 ml between 100 and 999Volume Binary Word 0 to The value is given in tenths Remaining 300 ml.The actual range therefore is 0.0 to 30.0 ml. Resolution: 0.5 ml BolusReady Binary Bit 7 0 or 1 The bit is 1 when the injector is ready for aninjection and both bolus parameters are >0. The bit is 0 at any othertime, including during a bolus. Infusion Binary Bit 6 0 or 1 The bit is1 when the injector Ready is ready for an injection and the infusionrate is > 0. The bit is 0 at any other time, including during aninfusion Bolus Binary Bit 5 0 or 1 The bit is 1 while the Runninginjector is performing a bolus. The bit is 0 at any other time. InfusionBinary Bit 4 0 or 1 The bit is 1 while the Running injector isperforming an infusion. The bit is 0 at any other time. Low VolumeBinary Bit 3 0 or 1 The bit is 1 if the programmed bolus volume is lessthan the volume remaining. If this condition becomes true during abolus, Low Volume will not be indicated until the bolus ends to avoidoperator confusion. The bit is 0 at any other time. Infusion Binary Bit2 0 or 1 The bit is 1 if an infusion Pending was interrupted by orrequested during a bolus and will resume after the bolus ends. The bitis 0 at any other time. Bolus Binary Bit 1 0 or 1 The bit is 1 when abolus Complete completes (programmed volume is delivered) . It is 0 atany other time. Note that the bit is only set for one message. Theexternal device is responsible for latching this information if desired.Injection Binary Bit 0 0 or 1 The bit is 1 when an injection aborted/canis aborted or canceled e.g. celed due to an invalid key press or runningout of volume. The bit is 0 at any other time. Note that the bit is onlyfor one status message. The exter- nal device is responsible forlatching this information if desired. Error Code ASCII Char ‘ ’ Threespaces indicate no [3] or error. The currently supported ‘A 1’ errorcodes are listed below: to P1: Perform check for air ‘Z99’ P2: No volumeremaining P3: Pressure stall P4: Syringe attached P5: Syringe removedS1: Disarm due to key press C: Critical Error ‘P’ codes require anoperator acknowledge, ‘S’ codes time out after five seconds ‘C’ requiresinjector power to be cycled.Layering

A summary of a preferred embodiment of the layering involved in thepresent example is presented in Table 6.

TABLE 6 Other Represent- Key Layer ative OSI Layer Functions/ServicesPreferred Methods Methods Layer 1.- Physical connections, RS-232.V28thinnet, Physical physical service data thicknet, Layer units (n-bitunshielded transmission), physical twisted connection end points, pairsequencing, data circuit (UTP), identification, fault RS-232-C,condition notification, FDDI, quality of service ISN, parameters (errorrates, wireless service availability, RF, transmission rates, wirelessdelays) infrared Layer 2.- Data link connection, Ack>/<Nak> messageEthernet, Data Link data link service data control, start of token Layerunits, error message <Stx> and ring, notification, flow end of message<Etx> HDLC control, quality of formatting, message service parametersnumbering scheme, transmit and receive retries (optional), duplicatemessage number detection and handling, CRC-16 error detection andcorrection operations Layer 3.- Data packet routing Not used InternetNetwork Protocol Layer (IP, SLIP, CSLIP, PPP), Internet Control MessageProtocol (ICMP), Internet Group Manage- ment Protoc0l (IGMP) Layer 4.-Error recovery and flow Not used Trans- Transport control, messagemission Layer multiplexing Control Protocol (TCP), User Diagram Protocol(UDP) Layer 5.- Control structure for Outgoing data is not RemoteSession managing communica- sent (session not Procedure Layer tions,session connection, initiated) unless Call session management, externaldevice (RPC) session termination, enables communica- interactionmanagement tion through CTS Layer 6.- Common operations on Messagecoding and External Presenta- the structure of the data decoding, dataData tion being exchanged, syntax folding Represen- Layer conversion,syntax tation negotiation, encryption, (XDR) compression Layer 7.-Communication manage- Fixed protocol, no SMTP, Applica- ment betweenapplica- negotiation. Injector SNMP, tion tions, synchronization of andimager share ftp, telnet, Layer applications, timing and control DNS,availability information to INS, NFS, determination, file perform theimaging arp, transfer access, job procedure. rlogin, transfer talk, ntp,traceroute

All medical products are regulated by government bodies in some way.This approval process includes validation and verification that theequipment performs properly under all conditions. As discussed above, itis possible that injector subsystem 15 a will be designed andmanufactured by one company and that imager subsystem 15 b will bedesigned and manufactured by another. In fact, there may be multiplemanufacturers for each. Subsystem interface 90 c may be manufactured byany of the above, or even be manufactured by a totally differentcompany. As also discussed above, the equipment functions may becoordinated by a human operator to perform the imaging needed todetermine the diagnosis. It is very difficult to test a piece ofequipment under all possible conditions when it has to communicate andcooperate with another piece of equipment. Even if two pieces ofequipment are manufactured by the same company, they are often designedby separate teams and there are thus still coordination and testingdifficulties. In addition, there may be a problem with changes orimprovements to one piece of equipment being compatible with older ornewer versions of the other equipment. It is, therefore, desirable thatstandard interfaces, such as the EIA RS-232.V28 standard be used in thepresent invention. To sufficiently isolate injector and imagersubsystems 15A and 15 b, it is preferred that subsystem interface 90 cbe powered separately and be isolated from both of the subsystems. Thishas a regulatory and validation benefit.

Although the present invention has been described in detail inconnection with the above embodiments and/or examples, it is to beunderstood that such detail is solely for that purpose. For example,many of the functions separately called out and described can beperformed by identical pieces of hardware. These and other variationscan be made by those skilled in the art without departing from thespirit of the invention except as it may be limited by the followingclaims.

1. A method for controlling an imaging procedure, comprising: providinga data interface in communicative connection with at least thepressurizing unit of an injector and an imaging unit to enable sharingof data comprising timing data and other data between the injector andthe imaging unit.
 2. The method of claim 1 wherein the controlling ofthe imaging procedure includes control of at least one of the following:the power in the signal sent into the patient, the time during which theenergy is applied to the patient, the gain of the amplifier whichreceives the signal from the patient, or the speed at which the energyis scanned across the patient.
 3. An injector system for producing acontrast-enhanced medical image of a patient in cooperation with animaging system, the imaging system applying energy to a patient andproducing an image or a measurement of a region of interest in thepatient from a signal resulting from the applied energy, the injectorcomprising: a source of a contrast or enhancement medium; a pressurizingsubsystem in connection with the source of contrast or enhancementmedium to pressurize the contrast or enhancement medium for injectioninto the patient; an injector control unit for controlling saidpressurizing subsystem; and a communication interface to exchangeinformation comprising timing data and other data between the injectorsystem and the imaging system.
 4. The injector system of claim 3 whereinthe communication is information transmitted from the injector system tothe imaging system.
 5. The injector system of claim 3 wherein thecommunications is information transmitted from the imaging system to theinjector system.
 6. The injector system of claim 5 wherein the injectorcontrol unit modifies one or more parameters of the injection based uponsaid information from the imaging system.
 7. The injector system ofclaim 5 wherein the injector control unit modifies one or moreparameters of the imaging system.
 8. The injector system of claim 7wherein the parameters being adjusted are chosen from the following: thepower in the energy sent into the patient, the time during which theenergy is applied to the patient, the gain of an amplifier whichreceives the signal from the patient, or the speed at which the energyis scanned across the patient.
 9. The injector system of claim 3 whereinthe control unit is adapted to adjust a condition of the contrast orenhancement medium flowing into the patient based directly upon thesignal resulting from the energy applied to the region of the patient.10. The injector system of claim 3 wherein the control unit is adaptedto adjust a condition of the contrast or enhancement medium flowing intothe patient to maintain at least one portion of the visual display at agenerally constant level of intensity.
 11. The injector system of claim3 wherein the control unit is adapted to control a dosage of the drug byadjusting a condition of the contrast or enhancement medium in thepatient.
 12. The injector system of claim 3 wherein the control unit isadapted to time injection of at least one bolus based on at least one ofthe states of at least a portion of the image or the signal resultingfrom the applied energy.
 13. The injector system of claim 3, furthercomprising an electrically isolated communication interface throughwhich the injector system exchanges information with the imaging system.14. The injector system of claim 3 wherein the exchange of informationbetween the injector system and the imaging system is bi-directional.15. An imaging unit for producing a contrast-enhanced medical image of apatient in cooperation with an injector system, the injector systempressurizing a contrast or enhancement medium for injection into thepatient, the imaging unit comprising: a source of a energy to be appliedto a region of interest in the patient; a display to provide an imagebased upon a signal resulting from the imaging energy applied to theregion of the patient; an imaging control unit for controlling theimaging unit; and a communication interface to exchange informationcomprising timing data and other data between the injector system andthe imaging unit.
 16. The imaging unit of claim 15 wherein thecommunication is information transmitted from the injector system to theimaging unit.
 17. The imaging unit of claim 15 wherein the communicationis information transmitted from the imaging unit to the injector system.18. The imaging unit of claim 15 wherein the imaging control unitmodifies one or more parameters of an injection based upon saidinformation from the imaging unit.
 19. The imaging unit of claim 15,further comprising an isolated interface through which the communicationinterface shares information with the injector system.
 20. The imagingunit of claim 15 wherein the exchange of information between theinjector system and the imaging unit is bi-directional.
 21. The methodof claim 1 wherein the data interface enables sharing of data in digitalformat between the injector and the imaging unit.
 22. The injectorsystem of claim 3 wherein the communication interface is adapted toexchange digital information between the injector system and the imagingsystem.
 23. The imaging unit of claim 15 wherein the communicationinterface is adapted to exchange digital information between theinjector system and the imaging unit.